Targeting Autophagy in Innate Immune Cells: Angel or Demon During Infection and Vaccination?

Sha Tao,Ingo Drexler

doi:10.3389/fimmu.2020.00460

Sha Tao, Ingo Drexler

Open Access

https://doi.org/10.3389/fimmu.2020.00460

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Abstract

Innate immune cells are the “doorkeepers” in the immune system and are important for the initiation of protective vaccine responses against infection. Being an essential regulatory component of the immune system in these cells, autophagy not only mediates pathogen clearance and cytokine production, but also balances the immune response by preventing harmful overreaction. Interestingly, recent literature indicates that autophagy is positively or negatively regulating the innate immune response in a cell type-specific manner. Moreover, autophagy serves as a bridge between innate and adaptive immunity. It is involved in antigen presentation by delivering pathogen compounds to B and T cells, which is important for effective immune protection. Upon infection, autophagy can also be hijacked by some pathogens for replication or evade host immune responses. As a result, autophagy seems like a double-edged sword to the immune response, strongly depending on the cell types involved and infection models used. In this review, the dual role of autophagy in regulating the immune system will be highlighted in various infection models with particular focus on dendritic cells, monocytes/macrophages and neutrophils. Targeting autophagy in these cells as for therapeutic application or prophylactic vaccination will be discussed considering both roles of autophagy, the “angel” enhancing innate immune responses, antigen presentation, pathogen clearance and dampening inflammation or the “demon” enabling viral replication and degrading innate immune components. A better understanding of this dual potential will help to utilize autophagy in innate immune cells in order to optimize vaccines or treatments against infectious diseases.

Highlights

The awarding of the Nobel Prize in 2016 to Yoshinori Ohsumi reflects the importance of autophagy in human health and disease
Three major ways can be distinguished: microautophagy, chaperonemediated autophagy, and macroautophagy. The latter has been intensively characterized in recent years because of its high impact on human health and disease [1]
Autophagy can be induced by two different arms of upstream signaling based on either mammalian target of rapamycin inactivation or adenosine monophosphate (AMP) activated protein kinase (AMPK) activation which leads to distinct Unc-51-like autophagy activating kinase 1 (ULK1) activation. mTOR typically responds to nutrient signals while adenosine monophosphate–activated protein kinase (AMPK) responds to the energy status of the cell

Summary

INTRODUCTION

The awarding of the Nobel Prize in 2016 to Yoshinori Ohsumi reflects the importance of autophagy in human health and disease. Autophagy is a homeostatic degradation process that enables cells to survive in case of stress, like accumulation of misfolded proteins and damaged organelles or starvation and energy deprivation. Mammalian cells deliver those “unwanted” materials to lysosomes for degradation. Three major ways can be distinguished: microautophagy, chaperonemediated autophagy, and macroautophagy. The latter has been intensively characterized in recent years because of its high impact on human health and disease [1]. We will focus on macroautophagy, referred to as autophagy in the following

Targeting Autophagy in Innate Immune Cells

VACCINES TARGETING AUTOPHAGY FOR EFFECTIVE ANTIGEN PROCESSING AND PRESENTATION

ADJUVANTS THAT ENHANCE VACCINE EFFICIENCY THROUGH AUTOPHAGY

THERAPEUTIC APPROACHES AGAINST INFECTIONS BY MODULATING AUTOPHAGY

FUTURE PROSPECTS